title: A surface-exposed neuraminidase affects complement resistance and virulence of the oral spirochaete Treponema denticola.
abstract: Neuraminidases (sialidases) catalyse the removal of terminal sialic acid from glycoconjugates. Bacterial pathogens often utilize neuraminidases to scavenge host sialic acid, which can be utilized either as a nutrient or as a decorating molecule to disguise themselves from host immune attacks. Herein, a putative neuraminidase (TDE0471) was identified in Treponema denticola, an oral spirochaete associated with human periodontitis. TDE0471 is a cell surface-exposed exo-neuraminidase that removes sialic acid from human serum proteins; it is required for T.denticola to grow in a medium that mimics gingival crevice fluid, suggesting that the spirochaete may use sialic acid as a nutrient in vivo. TDE0471 protects T.denticola from serum killing by preventing the deposition of membrane attack complexes on the bacterial cell surface. Animal studies revealed that a TDE0471-deficient mutant is less virulent than its parental wild-type strain in BALB/C mice. However, it causes a level of tissue damage similar to the wild type in complement-deficient B6.129S4-C3(tm1) (Crr) /J mice albeit the damage caused by both bacterial strains is more severe in these transgenic mice. Based on these results, we propose that T.denticola has evolved a strategy to scavenge host sialic acid using its neuraminidase, which allows the spirochaete to acquire nutrients and evade complement killing.
authors.affiliation: Department of Oral Biology, the State University of New York at Buffalo, New York, 14214, USA.
authors.forename: Kurni
authors.initials: K
authors.lastname: Kurniyati
authors.forename: Weiyan
authors.initials: W
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Chunhao
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D003470:Culture Media / Q000737:chemistry; D004195:Disease Models, Animal; D017353:Gene Deletion; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D048373:Treponema denticola / Q000201:enzymology* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D014211:Treponemal Infections / Q000382:microbiology / Q000473:pathology; D014774:Virulence
chemical_list: D001798:Blood Proteins; D003470:Culture Media; D008565:Membrane Proteins; D003165:Complement System Proteins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid